TarO : a target optimisation system for structural biology

This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC) Structural Proteomics of Rational Targets (SPoRT) initiative, (Grant BBS/B/14434). Funding to pay the Open Access publication charges for this article was provided by BBSRC.TarO (http://www.compbio.dundee.ac.uk/taro) offers a single point of reference for key bioinformatics analyses relevant to selecting proteins or domains for study by structural biology techniques. The protein sequence is analysed by 17 algorithms and compared to 8 databases. TarO gathers putative homologues, including orthologues, and then obtains predictions of properties for these sequences including crystallisation propensity, protein disorder and post-translational modifications. Analyses are run on a high-performance computing cluster, the results integrated, stored in a database and accessed through a web-based user interface. Output is in tabulated format and in the form of an annotated multiple sequence alignment (MSA) that may be edited interactively in the program Jalview. TarO also simplifies the gathering of additional annotations via the Distributed Annotation System, both from the MSA in Jalview and through links to Dasty2. Routes to other information gateways are included, for example to relevant pages from UniProt, COG and the Conserved Domains Database. Open access to TarO is available from a guest account with private accounts for academic use available on request. Future development of TarO will include further analysis steps and integration with the Protein Information Management System (PIMS), a sister project in the BBSRC Structural Proteomics of Rational Targets initiative.Publisher PDFPeer reviewe

Impacts of orography on large-scale atmospheric circulation

Some of the largest and most persistent circulation errors in global numerical weather prediction and climate models are attributable to the inadequate representation of the impacts of orography on the atmospheric flow. Existing parametrization approaches attempting to account for unresolved orographic processes, such as turbulent form drag, low-level flow blocking or mountain waves, have been successful to some extent. They capture the basic impacts of the unresolved orography on atmospheric circulation in a qualitatively correct way and have led to significant progress in both numerical weather prediction and climate modelling. These approaches, however, have apparent limitations and inadequacies due to poor observational evidence, insufficient fundamental knowledge and an ambiguous separation between resolved and unresolved orographic scales and between different orographic processes. Numerical weather prediction and climate modelling has advanced to a stage where these inadequacies have become critical and hamper progress by limiting predictive skill on a wide range of spatial and temporal scales. More physically-based approaches are needed to quantify the relative importance of apparently disparate orographic processes and to account for their combined effects in a rational and accurate way in numerical models. We argue that, thanks to recent advances, significant progress can be made by combining theoretical approaches with observations, inverse modelling techniques and high-resolution and idealized numerical simulations

The quiet editor: Ivan Vladislavić and South African cultural production

This article examines the literary and sociological significance of Ivan Vladislavić’s "double life” (Lahire, 2010: n.p.) as both editor and writer. With reference to a number of his editorial roles as well as the joint projects he has worked on with writers and visual artists, the article considers how Vladislavić’s work with others spreads symbolic value. Described by one of his clients as the “quiet editor”, Vladislavić can be read as a new kind of author; what he terms “creative editing” (Steyn, 2012: n.p.) as a new kind of writing, through which more traditional models of authorship and literary production are thrown into question — less Bourdieu’s (1984) “field of literary production” or Casanova’s (2004: 82) “world literary space”, red in tooth and claw, amd more Howard Becker’s “art world”: a convivial “network of cooperating people, all of whose work is essential to the final outcome” (1982: 25)

Summary of childhood asthma guidelines, 2021 : a consensus document

Asthma is the most common chronic illness of childhood. The prevalence is rising and the mortality and morbidity from asthma are unacceptably high in South Africa. It is important to make a correct diagnosis based, most importantly, on the clinical history and supported by investigations. The appropriate drug and device must be chosen to achieve good asthma control. Patients must be followed up regularly and their asthma control must be assessed. The treatment can then be adjusted according to the level of control. The COVID-19 pandemic has placed new challenges on the care of our asthmatics. Asthma education and adherence are important components of management of the condition.http://www.samj.org.zadm2022Paediatrics and Child Healt

Revival of the magnetar PSR J1622-4950: observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation.Comment: Published in ApJ (2018 April 5); 13 pages, 4 figure

A multidisciplinary study of a small, temporarily open/closed South African estuary, with particular emphasis on the influence of mouth state on the ecology of the system

In 2005/2006 a multidisciplinary research programme that included studies on the hydrodynamics, sediment dynamics, macronutrients, microalgae, macrophytes, zoobenthos, hyperbenthos, zooplankton, ichthyoplankton, fish and birds of the temporarily open/closed East Kleinemonde Estuary was conducted. Particular attention was given to the responses of the different ecosystem components to the opening and closing of the estuary mouth and how this is driven by both riverine and marine events. Using a complementary dataset of daily estuary mouth conditions spanning a 14-year period, five distinct phases of the estuary were identified, including closed (average = 90% of the days), outflow (<1%), tidal (9%) and semi-closed (<1%). The open-mouth phase is critical for the movements of a number of estuary-associated fish (e.g. Rhabdosargus holubi) and invertebrates (e.g. Scylla serrata) between the estuary and sea. The timing of this open phase has a direct influence on the ability of certain estuaryassociated fish (e.g. Lithognathus lithognathus) and invertebrates (e.g. Palaemon peringueyi) to successfully recruit into the system, with a spring opening (October/November) being regarded as optimal for most species. The type of mouth-breaching event and outflow phase is also important in terms of the subsequent salinity regime once the berm barrier forms. A deep mouth breaching following a large river flood tends to result in major tidal inputs of marine water prior to mouth closure and therefore higher salinities (15–25). Conversely, a shallow mouth breaching with reduced tidal exchange during the open phase often leads to a much lower salinity regime at the time of mouth closure (5–15). The biota, especially the submerged macrophytes, respond very differently to the above two scenarios, with Ruppia cirrhosa benefiting from the former and Potamogeton pectinatus from the latter. River flooding and the associated outflow of large volumes of water through the estuary can result in major declines in zooplankton, zoobenthos, hyperbenthos and fish populations during this phase. However, this resetting of the estuary is necessary because certain marine invertebrate and fish species are dependent on the opening of the estuary mouth in order to facilitate recruitment of larvae and post-larvae into the system from the sea. Slight increases in the numbers of certain piscivorous and resident wading bird species were recorded when the estuary mouth opened, possibly linked to increased feeding opportunities during that phase

Entanglement Entropy from a Holographic Viewpoint

The entanglement entropy has been historically studied by many authors in order to obtain quantum mechanical interpretations of the gravitational entropy. The discovery of AdS/CFT correspondence leads to the idea of holographic entanglement entropy, which is a clear solution to this important problem in gravity. In this article, we would like to give a quick survey of recent progresses on the holographic entanglement entropy. We focus on its gravitational aspects, so that it is comprehensible to those who are familiar with general relativity and basics of quantum field theory.Comment: Latex, 30 pages, invited review for Classical and Quantum Gravity, minor correction

Influence of crop residue ration supplementation on the attainment of puberty and postpartum reproductive activities of Red Sokoto goats

The general objective of this study was to come up with an appropriate, affordable and locally available crop residue supplementation package that would enhance reproductive performance in small ruminants. Specifically, 28 Red Sokoto weaner does between 3 and 4 months of age weighing between 2 and 3 kg were used in the first experiment to determine the influence of crop residue supplementation on age and weight at puberty as determined by blood progesterone levels. In the second experiment, another 28 adult does (equal to or greater than 2 years old) of the same breed in the same flock with lactation numbers between 1 and 3 were used to determine the length of postpartum acyclic period. In both experiments, a 3 x 2 factorial experimental design comprising three dietary supplements (A, B, C) at two feeding levels (1% and 2% of body weight) fed in addition to a basal diet of Digitaria smutsii hay and natural pasture ad libitum with an unsupplemented negative control group (D) and four goats per treatment was utilized. In ration A, a conventional concentrate supplement consisting of maize, wheat offal, cottonseed cake and bonemeal was utilized; in rations B and C, the supplement consisted of guinea-corn bran, cowpea husk and groundnut haulms; and maize offal, groundnut shells and groundnut haulms respectively. Unsupplemented (ration D) weaner does reached puberty at a later age and had lighter body weights than all the others. Weaner does on ration 2A (concentrate fed at 2% of body weight) attained puberty at the earliest age and heaviest body weight, although the age at puberty was not significantly different from those on rations 1A (concentrate fed at 1% body weight), 1C and 2C. Blood progesterone profiles before and after puberty ranged from 0.05 to 9.0 ng/ml, respectively, and was highest in does fed rations A and C and least in the unsupplemented does. The mean interval between kidding and initiation of ovarian activity was 54.28 plus or minus 17.61 days and the mean interval between kidding and conception was 63.04 plus or minus 25.34 days. Only 25% of the unsupplemented does conceived again during the period under study compared with 100% in rations 1A, 2A, 1C and 2C; 75% in ration 2B and 50% in ration 1B. It was concluded that implementation of supplementary feeding in the dry season improves reproductive performance in the Red Sokoto doe. Furthermore, ration C, a crop residue-based ration, was a suitable dry season supplementation alternative to the expensive conventional concentrate ration for the smallholder goat farmer in the subhumid tropics of Nigeria

Targeting pathogen metabolism without collateral damage to the host

The development of drugs that can inactivate disease-causing cells (e.g. cancer cells or parasites) without causing collateral damage to healthy or to host cells is complicated by the fact that many proteins are very similar between organisms. Nevertheless, due to subtle, quantitative differences between the biochemical reaction networks of target cell and host, a drug can limit the flux of the same essential process in one organism more than in another. We identified precise criteria for this â €network-based' drug selectivity, which can serve as an alternative or additive to structural differences. We combined computational and experimental approaches to compare energy metabolism in the causative agent of sleeping sickness, Trypanosoma brucei, with that of human erythrocytes, and identified glucose transport and glyceraldehyde-3-phosphate dehydrogenase as the most selective antiparasitic targets. Computational predictions were validated experimentally in a novel parasite-erythrocytes co-culture system. Glucose-transport inhibitors killed trypanosomes without killing erythrocytes, neurons or liver cells

A conceptual governance framework for climate change adaptation and disaster risk reduction integration

Climate change adaptation (CCA) and disaster risk reduction (DRR) have similar targets and goals in relation to climate change and related risks. The integration of CCA in core DRR operations is crucial to provide simultaneous benefits for social systems coping with challenges posed by climate extremes and climate change. Although state actors are generally responsible for governing a public issue such as CCA and DRR integration, the reform of top-down governing modes in neoliberal societies has enlarged the range of potential actors to include non state actors from economic and social communities. These new intervening actors require in-depth investigation. To achieve this goal, the article investigates the set of actors and their bridging arrangements that create and shape governance in CCA and DRR integration. The article conducts a comprehensive literature review in order to retrieve main actors and arrangements. The article summarizes actors and arrangements into a conceptual governance framework that can be used as a backdrop for future research on the topic. However, this framework has an explorative form, which must be refined according to site- and context-specific variables, norms, or networks. Accordingly, this article promotes an initial application of the framework to different contexts. Scholars may adopt the framework as a roadmap with which to corroborate the existence of a theoretical and empirical body of knowledge on governance of CCA and DRR integration